The invention relates to the use of α-lactalbumin for promoting the cellular absorption of glucose, improving the regulation of glycemia and/or preventing the appearance of insulin resistance and/or type II diabetes. To this effect, the α-lactalbumin can be used in a composition intended to be absorbed enterally or parenterally, whether it is a composition of dietary, dietetic or pharmaceutical type.
Insulin resistance is defined by a reduction in the biological response to the action of insulin and is reflected by a reduced effectiveness of insulin on its target tissues.
Its cause is multifactoral and very complex, and involves the simultaneous intervention of environmental factors and endogenous factors of genetic origin (Pessin J. and Saltiel A. R., 2000, J. Clin. Invest., 106, 165-169).
In the short term, insulin resistance leads to an imbalance in energy metabolism which manifests itself through the phenomenon of postprandial hyperglycemia. In the long term, type II diabetes is the major consequence of insulin resistance.
Type II diabetes is characterized by chronic hyperglycemia without having eaten and abnormally high transient hyperglycemia after the ingestion of a carbohydrate load. This poor regulation of glycemia reflects a weak reaction, by the tissues that perform glucose uptake and metabolism, to the insulin signal (insulin resistance). Hyperglycemia is responsible for the many complications associated with diabetes, at the microvascular or macrovascular level.
In reality, the decreased capacity for regulating glycemia is a gradual phenomenon and a reduced sensitivity to insulin is a prepathological step that marks a considerable risk of developing diabetes. The nature of the diet affects the appearance of a reduced sensitivity to insulin, but the influence of the amount and of the nature of the proteins in the diet has remained relatively unexplored.
The favorable action of fish proteins, in particular of cod proteins, in the regulation of glycemia, the improvement of glucose tolerance and the prevention of the appearance of insulin resistance has been demonstrated in the studies by C. Lavigne et al., Am. J. Physiol. Endocrin. Metab. 281: E62-E71, 2001; F. Tremblay et al., Diabetes. 52: 29-37, 2003; C. Lavigne et al., Am. J. Physiol. Endocrin. Metab. 278: E491-E500, 2000.
Fish proteins are found to be more effective than soybean proteins and casein, although their amino acid compositions are relatively similar. The use of fish proteins in a dietary, dietetic or pharmaceutical composition as an additive for improving the cellular absorption of glucose and/or the regulation of glycemia has, however, several drawbacks:
The fish protein fractionation industry is not currently at a very advanced level of development, in particular by comparison with the soybean or milk industry. The extraction of such proteins from fish meat would cause the latter to lose most of its market value, thereby resulting in prohibitive costs.
An objective of the present invention was to find a product having the properties of regulating glycemia, promoting the cellular absorption of glucose, improving insulin sensitivity, and/or preventing the appearance of type II diabetes. A product which is both easy to prepare and economical and can be readily used as a food additive without harming the gustatory and/or olfactory qualities of the food into which it is incorporated was sought.
A subject of the present invention is the use of α-lactalbumin in a dietary composition or for the preparation of a pharmaceutical composition as a glycemia-regulating agent, for promoting the cellular absorption of glucose and/or for preventing the appearance of type II diabetes. α-lactalbumin is a milk protein. It is the second most predominant protein of milk serum, or lactoserum, in terms of its percentage by weight, after lactoferrin or β-lactoglobulin for human milk or bovine milk, respectively.
Document WO 02/064090 discloses a food supplement containing milk serum proteins enriched in α-lactalbumin, a low-glycemic-index sugar, fats, caffeine and a source of 5-hydroxytryptophan. This food supplement is intended for individuals in a state of stress. It makes it possible to increase the serotonin level in an individual. The low-glycemic-index sugars enable delayed glucose and insulin release. The α-lactalbumin promotes the increase in serotonin by providing tryptophan which is a serotonin precursor.
In addition, document EP-1 228 707 discloses the use of α-lactalbumin or of an α-lactalbumin-enriched milk serum protein concentrate as a prebiotic food or as a food supplement or additive. The use of α-lactalbumin is intended to reinforce the intestinal microbial population by promoting its growth. These food supplements can be used for the treatment of gastroenteritis.
Document U.S. Pat. No. 6,156,738 describes the use of food supplements in the form of bars comprising simple sugars, proteins, lipids and complex sugars. These food supplements make it possible to regulate nocturnal hypoglycemia in insulin-dependent diabetics. Milk serum and lactalbumin are mentioned among the proteins that can be used. The mechanism of function proposed by the authors is the following: the sugars are released in 3 phases over the course of the night: rapid release of the simple sugars, release of sugars from the proteins converted by the liver, release of the slow sugars. In this document, the general term lactalbumin is used to denote lactoserum (total) proteins and not α-lactalbumin.
In addition, the proteins are used in these food supplements as a source of sugars and not as a regulator of the assimilation of glucose originating from another source. Consequently, the use of α-lactalbumin for promoting glucose assimilation and/or regulating glycemia and/or preventing the appearance of type II diabetes and/or preventing insulin resistance is neither mentioned nor suggested by this document.
α-lactalbumin has also been mentioned for its potential role as an anticarcinogenic agent (G. H. McIntosh et al., Int. Dairy Journal, 5: 425-434, 1998), and as a food additive for preventing lipid oxidation and promoting the reduction of adipose tissues (J-C. J. Bouthegourd et al., Am. J. Physiol. Endocrinol. Metab., 283: E565-E572, 2002). It is also known, by virtue of the article “Les propriétés des protéins de petit lait” [The properties of whey proteins] Nutranews Jan. 11, 2003, that caseins and lactoserum proteins inhibit the renin-angiotensin-aldosterone system and, in this respect, would have the capacity to reduce body fat and also the diseases which are associated therewith, such as type II diabetes (G. H. Gossens et al., Obesity Reviews, 4: 43, 2003). However, this document does not mention a particular capacity of α-lactalbumin for preventing or treating insulin resistance and/or type II diabetes.
Finally, glutathione is capable of modulating oxidative stress, and a hypothesis regularly proposed consists in attributing the deleterious effects of poor glycemic control to the oxidizing role of glucose (A. Ceriello et al., Diabetes Care, 25: 1439, 2002). In addition, studies have shown that glutathione can modulate glucose tolerance or insulin sensitivity (G. Paolisso et al., Am. J. Physiol. 263: E435, 1992; M. Khamaisi et al., Biochem. J., 349: 579, 2000). Consequently, since the cysteine content in the diet acutely and chronically influences the glutathione content of the organism (L. C. Lands et al., J. Appl. Physiol. 87: 1381, 1999; M. H. Stipanuk et al., J. Nutr. 132: 3369, 2002), it was possible to put forward the hypothesis that α-lactalbumin, simply by virtue of its cysteine content, was capable of limiting oxidative stress and of promoting insulin sensitivity, and could therefore curb the prepathological progression of glucose intolerance. However, tests disclosed in the experimental section show that the mere cysteine content of α-lactalbumin is not sufficient to explain the action of this protein on the regulation of glycemia and glucose tolerance.